MECHANISM OF SUPPRESSION OF REPRODUCTIVE FUNCTION BY STRESS: ELECTROPHYSIOLOGICAL STUDY

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Under stress conditions, reproductive function is known to be suppressed. In the present study, the effect of tumor necrosis factor (TNF), which is secreted from macrophages and astrocytes in response to invasive stimuli, on the electrical activity of the hypothalamic gonadotropin-releasing hormone (GnRH) pulse generator was studied in the rat by means of multiunit activity (MUA) recording techniques. Characteristic increases (volleys) in MUA associated with pulsatile secretion of luteinizing hormone (LH). were recorded during a pretreatment control period. After either intravenous or intraventricular injection of TNF, MUA volleys occurred at regular intervals for about one hour, but thereafter the interval was prolonged for a few hours and then returned to control levels. These changes in MUA volleys were faithfully reflected by the pulsatile LH secretion. On the other hand, pretreatment with indomethacin blocked the effect of TNF on the interval between the MUA volleys. These results suggest that TNF, produced either in the peripheral tissue or in the brain, leads to a decrease in GnRH pulse frequency with a resultant suppression of reproductive function, and that the TNF action on hypothalamic GnRH pulse generator may be mediated by prostaglandins.